The overall aims of this proposal are to investigate the role of histamine as a regulator of immune reactions. While the physiologic role of histamine as a mediator of allergic reactions is well known, its ability to modulate humoral or cellular-immune phenomena has only recently been appreciated. Results derived from this line of investigation may provide a better insight into the basic control mechanisms of immunity and might lead to improve forms of therapy for patients having immunologic defects. For example, pharmacologic manipulation of the immune response in the latter patients could be a reality since there are already available several selective histamine antagonists that are being used clinically. The specific areas of investigation are: 1) further studies of the lymphokine, histamine-induced suppressor factor of HSF, in terms of its physico-chemical characterization, defining the subset of lymphocytes that produce the factor, the conditions for its production, and its mechanism of action; 2) an investigation into newly described lymphokine, histamine-releasing factor or HRF, in terms of its physico-chemical characterization, defining the subpopulation of cells responsible for its production, its mechanism of action, and its interrelationship with HSF; 3) an investigation into a lymphokine, histamine-induced chemotactic inhibitor or HCI, with regard to the cells that produce it, the conditions for its production and its mechansim of action; 4) in vivo studies in a guinea pig model in which the ability of selective histamine antagonists to alter both humoral cellular immune responses will be investigated. Cell transfer experiments will be employed to determine what effect the absence of cells bearing histamine receptors will have on a given immune response. We also hope to evaluate the in vivo effects of some of the lymphokines produced in vitro.